Effects of victimization on mental health and substance use trajectories in young sexual minority men.
Young sexual minority men (YSMM) experience more victimization and are at higher risk for mental health and substance use problems compared with heterosexual youth. We attempt to understand change over time in the experience of these constructs among YSMM. Data were taken from a diverse community-based sample of YSMM (N = 450, baseline mean age 18.93) surveyed every 6 months for 2.5 years. Multilevel modeling was used to model within-person change in victimization, internalizing symptoms, externalizing symptoms, alcohol frequency, marijuana use, and illicit drug use. We tested the indirect effect of concurrent and time-lagged victimization on the association between age and mental health and substance use. Victimization, internalizing symptoms, and externalizing symptoms decreased over time. Concurrent victimization was associated with higher internalizing symptoms, externalizing symptoms, alcohol use, marijuana use, and illicit drug use. Analysis of indirect effects suggested that the association between victimization and mental health and substance use outcomes decreased as participants transitioned from adolescence into adulthood. This study found that the reduction in victimization that YSMM experience as they grow older is associated with a reduction in negative mental health and substance use outcomes. Prevention efforts to limit victimization exposure may reduce health disparities for YSMM.


A comparison of stresses in implantation for grafted and plate-and-screw mandible reconstruction.
During oral rehabilitation by dental implantation for mandibles reconstructed with plate and screws, intensified stresses can develop at the implant-bone interfaces and fixation screw-bone interfaces that might cause complications at these interfaces. The present study aims to evaluate the stresses occurring at these sites using the finite element method. Ten computer-aided design models simulating 10 mandibles were produced and were termed normal models. Simulation surgery was performed on these normal models, where parts of the models were removed and replaced by fibula or reconstruction plates plus screws. Depending on the replaced part (body [B] or body and symphysis [BS]) and the reconstruction materials (fibula [Fib] or reconstruction plate [Plate]), the modified models were termed B-Fib, B-Plate, BS-Fib, and BS-Plate models, respectively. For each model, an implant was embedded in the first molar region. Stresses occurring at the implant-bone interfaces and fixation screw-bone interfaces on mastication were calculated using the finite element method and compared among the model groups. The stresses at the implant-bone interfaces showed no statistically significant differences among the 5 model groups. With the B-Plate and BS-Plate models, stresses at the fixation screw-bone interfaces were nearly twice as intense as those at the implant-bone interfaces. If it is allowed that complication risks correlate with stresses, fixation screws are more subject to failure than implants in performing implantation for mandibles reconstructed with a plate and fixation screws. Therefore, the fixation screws deserve special attention in performing oral rehabilitation for such patients.


The effect of vigorous treadmill exercise on plasma lipoproteins and hepatic lipoprotein production in Zucker rats.
Chronic exercise has been shown to alter plasma lipids in man and animals, but the mechanism(s) responsible for this phenomenon have not been clarified. In the present study we have examined the role of the liver in the production of lipoproteins following an intensive exercise regimen in lean and obese Zucker rats. Four-week-old lean and obese male Zucker rats were subjected to a vigorous exercise regimen of running on a motor-driven treadmill for 10 weeks. Hepatic lipoprotein cholesterol production was then assessed using liver perfusion techniques. Plasma cholesterol concentration was significantly lower in both lean and obese runners versus appropriate non-exercised controls. This decrease was due to a decline in both chylomicron and HDL cholesterol. Exercise had no affect on plasma VLDL and LDL cholesterol concentrations. Hepatic VLDL cholesterol production was elevated in obese rats versus lean rats and was not affected by exercise in runners of either phenotype. Hepatic HDL cholesterol production was higher in lean runners but was unchanged in obese runners. Plasma triglyceride was reduced by 50% in exercised obese rats. In summary, intense exercise decreased plasma triglyceride, cholesterol, and HDL cholesterol concentrations in lean and obese Zucker rats. Since hepatic HDL cholesterol production was increased and hepatic VLDL cholesterol production was unaffected by exercise, the changes in plasma lipid levels observed following exercise appear to be mediated by extrahepatic mechanisms.


Altered estrogen receptor expression in skeletal muscle and adipose tissue of female rats fed a high-fat diet.
Estrogen receptors (ERs) are expressed in adipose tissue and skeletal muscle, with potential implications for glucose metabolism and insulin signaling. Previous studies examining the role of ERs in glucose metabolism have primarily used knockout mouse models of ERα and ERβ, and it is unknown whether ER expression is altered in response to an obesity-inducing high-fat diet (HFD). The purpose of the current study was to determine whether modulation of glucose metabolism in response to a HFD in intact and ovariectomized (OVX) female rats is associated with alterations in ER expression. Our results demonstrate that a 6-wk HFD (60% calories from fat) in female rats induces whole body glucose intolerance with tissue-specific effects isolated to the adipose tissue, and no observed differences in insulin-stimulated glucose uptake, GLUT4, or ERα protein expression levels in skeletal muscle. In chow-fed rats, OVX resulted in decreased ERα with a trend toward decreased GLUT4 expression in adipose tissue. Sham-treated and OVX rats fed a HFD demonstrated a decrease in ERα and GLUT4 in adipose tissue. The HFD also increased activation of stress kinases (c-jun NH₂-terminal kinase and inhibitor of κB kinase β) in the sham-treated rats and decreased expression of the protective heat shock protein 72 (HSP72) in both sham-treated and OVX rats. Our findings suggest that decreased glucose metabolism and increased inflammation in adipose tissue with a HFD in female rats could stem from a significant decrease in ERα expression.


Potential Impact of Incorporating a Patient-Selected Support Person into mHealth for Depression.
Although telephone care management improves depression outcomes, its implementation as a standalone strategy is often not feasible in resource-constrained settings. Moreover, little research has examined the potential role of self-management support from patients' trusted confidants. To investigate the potential benefits of integrating a patient-selected support person into automated mobile health (mHealth) for depression. Patient preference trial. Depressed primary care patients who were at risk for antidepressant nonadherence (i.e., Morisky Medication Adherence Scale total score > 1). Patients received weekly interactive voice response (IVR) telephone calls for depression that included self-management guidance. They could opt to designate a lay support person from outside their home to receive guidance on supporting their self-management. Patients' clinicians were automatically notified of urgent patient issues. Each week over a period of 6 months, we used IVR calls to monitor depression with the Patient Health Questionnaire-9 (PHQ-9; with total < 5 classified as remission), adherence (single item reflecting perfect adherence over the past week), and functional impairment (any bed days due to mental health). Of 221 at-risk patients, 61% participated with a support person. Analyses were adjusted for race, medical comorbidity, and baseline levels of symptom severity and adherence. Significant interaction effects indicated that during the initial phase of the program, only patients who participated with a support person improved significantly in their likelihood of either adhering to antidepressant medication (AOR = 1.31, 95% CI: 1.16-1.47, p < 0.001) or achieving remission of depression symptoms (AOR = 1.24, 95% CI: 1.14-1.34, p < 0.001). These benefits were maintained throughout the 6-month observation period. Incorporating the "human factor" of a patient-selected support person into automated mHealth for depression self-management may yield sustained improvements in antidepressant adherence and depression symptom remission. However, this needs to be confirmed in a subsequent randomized controlled trial.


Intradural extramedullary spinal masses treated at the Wits teaching hospitals between 2014 - 2017.
Intradural extramedullary (IDEM) spinal masses are common lesions with varying histological diagnoses often associated with significant neurological deficits. This study aimed to describe the epidemiology, management and perioperative outcome of IDEM tumours seen at the teaching hospitals of the University of the Witwatersrand, Johannesburg, between 2014 and 2017. 92 patients were included in the study. The ages ranged from 21 to 87 years, sex ratio was M:F 1:1.4, and duration of symptoms prior to diagnosis ranged between 3 days to 18 months. Local and radicular type pain as well as motor weakness were the commonest symptoms. 67% had severe neurological deficit McCormick Grade III and IV. Schwannoma (26) Neurofibromas (21) and Meningiomas (16) and were the most frequent tumour types. Meningiomas predominantly occurred at the cranio-cervical and thoracic levels. Nerve sheath tumours were mostly found at the cervical and lumbar levels while filum terminale ependymomas occurred at the thoracolumbar area. Laminectomy was the commonest surgical approach employed, and the extent of resection varied, with total excision in half the cases. Neurological function was regained in 3 patients, deteriorated in two and was unchanged in the remainder. IDEM tumours are an important subset of spinal cord compressive lesions Presentation with severe neurological deficit is common and though resection is feasible neurological deficit remains in the vast majority. Earlier detection should improve the results of surgery.


Hydroxyapatite and titania sol-gel composite coatings on titanium for hard tissue implants; mechanical and in vitro biological performance.
Hydroxyapatite (HA) composites with titania (TiO2) up to 30 mol % were coated on a titanium (Ti) substrate by a sol-gel route, and the mechanical and biological properties of the coating systems were evaluated. Using polymeric precursors, highly stable HA and TiO2 sols were prepared prior to making composite sols and coatings. Coatings were produced under a controlled spinning and heat treatment process. Pure phases of HA and TiO2 were well developed on the composites after heat treatment above 450 degrees C. The HA-TiO2 composite coating layers were homogeneous and highly dense with a thickness of about 800-900 nm. The adhesion strength of the coating layers with respect to Ti substrate increased with increasing the TiO2 addition. The highest strength obtained was as high as 56 MPa, with an improvement of about 50% when compared to pure HA (37 MPa). The osteoblast-like cells grew and spread actively on all the composite coatings. The proliferation and alkaline phosphatase (ALP) activity of the cells grown on the composite coatings were much higher than those on bare Ti, and even comparable to those on pure HA coating. Notably, the HA-20% TiO2 composite coating showed a significantly higher proliferation and ALP expression compared to bare Ti (p < 0.05). These findings suggest that the sol-gel-derived HA-TiO2 composite coatings possess excellent properties for hard tissue applications from the mechanical and biological perspective.


A codesigned integrated kidney and diabetes model of care improves patient activation among patients from culturally and linguistically diverse backgrounds.
Little is known about the relationship between patients' cultural and linguistic backgrounds and patient activation, especially in people with diabetes and chronic kidney disease (CKD). We examined the association between culturally and linguistically diverse (CALD) background and patient activation and evaluated the impact of a codesigned integrated kidney and diabetes model of care on patient activation by CALD status in people with diabetes and CKD. This longitudinal study recruited adults with diabetes and CKD (Stage 3a or worse) who attended a new diabetes and kidney disease service at a tertiary hospital. All completed the patient activation measure at baseline and after 12 months and had demographic and clinical data collected. Patients from CALD backgrounds included individuals who spoke a language other than English at home, while those from non-CALD backgrounds spoke English only as their primary language. Paired t-tests compared baseline and 12-month patient activation scores by CALD status. Patients from CALD backgrounds had lower activation scores (52.1 ± 17.6) compared to those from non-CALD backgrounds (58.5 ± 14.6) at baseline. Within-group comparisons showed that patient activation scores for patients from CALD backgrounds significantly improved by 7 points from baseline to 12 months follow-up (52.1 ± 17.6-59.4 ± 14.7), and no significant change was observed for those from non-CALD backgrounds (58.5 ± 14.6-58.8 ± 13.6). Among patients with diabetes and CKD, those from CALD backgrounds report worse activation scores. Interventions that support people from CALD backgrounds with comorbid diabetes and CKD, such as the integrated kidney and diabetes model of care, may address racial and ethnic disparities that exist in patient activation and thus improve clinical outcomes. Patients, caregivers and national consumer advocacy organisations (Diabetes Australia and Kidney Health Australia) codesigned a new model of care in partnership with healthcare professionals and researchers. The development of the model of care was informed by focus groups of patients and healthcare professionals and semi-structured interviews of caregivers and healthcare professionals. Patients and caregivers also provided a rigorous evaluation of the new model of care, highlighting its strengths and weaknesses.


Iodine-125 implant and external beam irradiation in patients with localized pancreatic carcinoma: a comparative study to surgical resection.
Twelve patients with biopsy-proven clinically localized ductal pancreatic cancers (less than 7 cm in greatest diameter) judged unsuitable for resection were treated by bypass surgery, an Iodine-125 implant (20-39 mCi), and postoperative irradiation (4000-4500 rads). The potential problems of significant bleeding, pancreatic fistula, or pancreatitis were not experienced. A local recurrence developed in one patient and two recurred in regional lymph nodes. The projected median survival of the group is 11 months with four of the 12 patients still surviving. For purposes of comparison all patients with pancreatic ductal carcinoma treated by radical resection during a similar time were evaluated. All ten have died with a median survival of six months. Twelve of 22 (55%) of the combined implanted and resected groups have developed distant metastasis. Further pursuit of intraoperative techniques of irradiation in combination with adjuvant multidrug chemotherapy seems indicated in an attempt to prolong patient survival which is now limited by hematogenous metastases.


Comparing the effect of temporal delay on the availability of egocentric and allocentric information in visual search.
Frames of reference play a central role in perceiving an object's location and reaching to pick that object up. It is thought that the ventral stream, believed to subserve vision for perception, utilises allocentric coding, while the dorsal stream, argued to be responsible for vision for action, primarily uses an egocentric reference frame. We have previously shown that egocentric representations can survive a delay; however, it is possible that in comparison to allocentric information, egocentric information decays more rapidly. Here we directly compare the effect of delay on the availability of egocentric and allocentric representations. We used spatial priming in visual search and repeated the location of the target relative to either a landmark in the search array (allocentric condition) or the observer's body (egocentric condition). Three inter-trial intervals created minimum delays between two consecutive trials of 2, 4, or 8seconds. In both conditions, search times to primed locations were faster than search times to un-primed locations. In the egocentric condition the effects were driven by a reduction in search times when egocentric information was repeated, an effect that was observed at all three delays. In the allocentric condition while search times did not change when the allocentric information was repeated, search times to un-primed target locations became slower. We conclude that egocentric representations are not as transient as previously thought but instead this information is still available, and can influence behaviour, after lengthy periods of delay. We also discuss the possible origins of the differences between allocentric and egocentric priming effects.


Degradation of NTO induced by superoxide and hydroperoxyl radicals: a comprehensive DFT study.
Reactive oxygen species, produced in the aquatic environment under sunlight irradiation, actively take part in degradation of environmental pollutants. NTO (5-nitro-1,2,4-triazol-3-one), being a primary ingredient in a suite of insensitive munitions formulations, may be released into training range soils after incomplete detonations and dissolved in surface water and groundwater due to good water solubility. A detailed investigation of a possible mechanism for NTO decomposition in water induced by superoxide and hydroperoxyl radicals as one of the pathways for NTO environmental degradation was performed with a computational study at the PCM(Pauling)/M06-2X/6-311++G(d,p) level. Superoxide causes rapid deprotonation of NTO. Decomposition of NTO induced by hydroperoxyl radicals was found to be a multistep process leading to mineralization of the nitrocompound. The reaction process may begin with hydroperoxyl radical attachment to carbon atom of the CN double bond of NTO, then proceeds through rupture of C-N bonds and addition of water molecules leading to the formation of nitrous acid, ammonia, nitrogen gas, hydrazine, and carbon(IV) oxide. The obtained results indicate that the anionic form of NTO shows a higher reactivity towards hydroperoxyl radicals than its neutral form. Excitation of NTO by sunlight enables complete mineralization of NTO induced by superoxide. The calculated activation energies and exergonicity of the studied processes support the contribution of hydroperoxyl radicals and superoxide to the degradation of NTO in the environment into low-weight inorganic compounds.


Plastic surgery and smoking: a prospective analysis of incidence, compliance, and complications.
Tobacco use remains a persistent risk factor in elective plastic surgery. Although nicotine is thought to increase complications, which procedures are affected and the reliability of patient-provided histories remain poorly defined. The authors sought to examine nicotine use and its impact on outcomes. All patients in a single-surgeon practice undergoing surgery with general anesthesia during a 2-year period were enrolled. Preoperative evaluation included a thorough smoking history. All patients had urine samples taken on the day of surgery to assess for nicotine metabolites. Patients were followed for a minimum of 3 months after surgery and monitored for complications. Four hundred fifteen patients were enrolled. Of these, 139 (33.5 percent) stated that they had quit smoking and 39 (9.4 percent) were admitted active smokers. For the 362 patients with urine nicotine analysis available, 54 showed active smoking. Fifteen of these (4.1 percent) had denied current tobacco use. Patients stating that they had quit smoking were more likely to be deceitful than those stating they had never smoked (p < 0.001). Smokers had significantly higher overall complication rates (OR, 3.7; p < 0.001) and tissue necrosis rates (OR, 4.3; p = 0.02) and were likelier to require reoperation (OR, 3.7; p < 0.001). In a large cohort study examining the prevalence and impact of nicotine in the general plastic surgery population, substantial rates of deception regarding smoking status were found. Furthermore, active smoking was strongly correlated with complications. A methodologic approach to the detection and management of patients using tobacco products can help to optimize outcomes. Risk, II.


Determination and Kinetic Characterization of a New Potential Inhibitor for AmsI Protein Tyrosine Phosphatase from the Apple Pathogen Erwinia amylovora.
Erwinia amylovora is a Gram-negative bacterium, responsible for the fire blight disease in Rosaceae plants. Its virulence is correlated with the production of an exopolysaccharide (EPS) called amylovoran, which protects the bacterium from the surrounding environment and helps its diffusion inside the host. Amylovoran biosynthesis relies on the expression of twelve genes clustered in the ams operon. One of these genes, amsI, encodes for a Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) called EaAmsI, which plays a key role in the regulation of the EPS production pathway. For this reason, EaAmsI was chosen in this work as a target for the development of new antibacterial agents against E. amylovora. To achieve this aim, a set of programs (DOCK6, OpenEye FRED) was selected to perform a virtual screening using a database of ca. 700 molecules. The six best-scoring compounds identified were tested in in vitro assays. A complete inhibition kinetic characterization carried out on the most promising molecule (n-Heptyl β-D-glucopyranoside, N7G) showed an inhibition constant of 7.8 ± 0.6 µM. This study represents an initial step towards the development of new EaAmsI inhibitors able to act as antibacterial agents against E. amylovora infections.


Demonstration of a saturable binding site for thyrotropin in Yersinia enterocolitica.
Several lines of evidence suggest that there might be immunologic cross-reactivity between the thyroid plasma membrane in humans and antigenic determinants in the enteric pathogen Yersinia enterocolitica. Studies were therefore performed to determine whether Y. enterocolitica, like the thyroid membrane, contains a thyrotropin binding site. A saturable binding site for bovine thyrotropin was indeed demonstrable, particularly in preparations of the organism that have been treated with ethylenediaminetetraacetate and lysozyme. Hormonal specificity of the binding site, as judged from the inhibition of binding of 125I-labeled bovine thyrotropin, was similar to that of the thyrotropin receptor in human thyroid tissue.


CXCL12 (SDF-1)/CXCR4 pathway in cancer.
Chemokines, small proinflammatory chemoattractant cytokines that bind to specific G-protein-coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. The chemokine CXCL12 [stromal cell-derived factor-1 (SDF-1)] binds primarily to CXC receptor 4 (CXCR4; CD184). The binding of CXCL12 to CXCR4 induces intracellular signaling through several divergent pathways initiating signals related to chemotaxis, cell survival and/or proliferation, increase in intracellular calcium, and gene transcription. CXCR4 is expressed on multiple cell types including lymphocytes, hematopoietic stem cells, endothelial and epithelial cells, and cancer cells. The CXCL12/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival. This pathway is a target for therapeutics that can block the CXCL12/CXCR4 interaction or inhibit downstream intracellular signaling.


State of the art: Transforaminal approach for percutaneous endoscopic lumbar discectomy under local anesthesia.
Minimally invasive percutaneous endoscopic discectomy (PED) with a transforaminal approach under local anesthesia was started in the late 20th century. As the procedure requires a skin incision of only 8 mm, it is the least invasive disc surgery procedure at present, and owing to advances in instruments and optics, the use of this technique has gradually spread. In Japan, Dr. Dezawa from Teikyo University Mizonokuchi Hospital introduced this technique in 2003. Thanks to his efforts, the number of surgeons who can perform PED has increased, although the number of active PED surgeons is still only around 20. The first author (K.S.) started PED in 2010. In this review article, we explain the state-of-the-art PED transforaminal technique for minimally invasive disc surgery and present three successful cases.


Restricted translation of the genome of the flavivirus Kunjin in vitro.
Virion RNA of Kunjin virus was translated in rabbit reticulocyte lysates at a rate (7000 daltons/min) approaching that observed previously in vivo. As many as 18 polypeptides were translated and shown by tryptic peptide mapping to be closely related to one another and to contain some of the elements of envelope (E) and most of the elements of core (C) proteins of Kunjin virus. None of the products resolved in gels were precipitated by antiserum to purified E protein, but the larger products were precipitated by an antiserum against all the Kunjin virus-specified proteins. No evidence was obtained of translation of the non-structural proteins, despite attempts to retain or perturb the structure of the virion RNA. As many as 50% of the amino acid sequences in the peptide maps were not identifiable.


Loss of adipose tissue and plasma phospholipids: relationship to survival in advanced cancer patients.
Extensive loss of adipose tissue is a key feature of cancer cachexia. Advanced cancer patients also exhibit low plasma phospholipids. It is not known whether these processes coincide across the cancer trajectory nor has their relationship with survival been defined. Changes in adipose tissue mass and plasma phospholipids were characterized within 500days prior to death and prognostic significance assessed. Adipose tissue rate of change was determined in a retrospective cohort of patients who died of colorectal and lung cancers (n=108) and who underwent >2 computed tomography scans in the last 500days of life. Plasma phospholipid fatty acids were measured prospectively in a similar cohort of patients with metastatic cancer (n=72). Accelerated loss of adipose tissue begins at 7months from death reaching an average loss of 29% of total AT 2months from death. Plasma phospholipid fatty acids were 35% lower in patients closest to death versus those surviving >8months. Losses of phospholipid fatty acids and adipose tissue occur in tandem and are predictive of survival. Depletion of plasma phospholipids likely indicates a deficit of essential fatty acids in the periphery which may contribute to loss of adipose tissue.


Developing an enforceable "right to treatment" theory for the chronically mentally disabled in the community.
Historical developments, mental health approaches, and applicable legal authorities are examined in arguing a legal basis for pursuing greater treatment benefits for chronically mentally disabled persons in the community. Mental health lawyers have traditionally been concerned with patients' right to treatment while in the hospital. Lawyers are called on to examine the plight of (and to extend advocacy for) the chronically mentally disabled in the community.


MiR-338-3p inhibits the growth and invasion of non-small cell lung cancer cells by targeting IRS2.
MicroRNA-338-3p (miR-338-3p) has recently been reported to have anti-cancer efficacy in several types of cancers. However, its biological function and underlying mechanism involved in modulation of human non-small cell lung cancer (NSCLC) remain largely unknown. The present study was designed to investigate the function and underlying mechanism of miR-338-3p in human NSCLC tissues and cell lines. We demonstrated that miR-338-3p was significantly decreased in NSCLC tissues and cell lines, and negatively correlated with advanced and tumor-node-metastasis (TNM) stage and lymph node metastasis (both P<0.01). Transient overexpression of miR-338-3p by transfecting with miR-338-3p mimic significantly suppressed NSCLC cell proliferation, migration, invasion and induced apoptosis and cell cycle at G1 phase. Additionally, insulin receptor substrate 2 (IRS2), a known oncogene, was identified as a potential target gene of miR-338-3p. Subsequent investigations found a negative correlation between the expression of miR-338-3p and IRS2 in NSCLC tissues. Furthermore, overexpression of IRS2 reversed the effects of miR-338-3p in NSCLC cells on cell proliferation, cycle, apoptosis, migration, invasion. These findings suggested that miR-338-3p might act as a tumor suppressor by directly targeting IRS2 in NSCLC.


The Ring-Type E3 Ubiquitin Ligase JUL1 Targets the VQ-Motif Protein JAV1 to Coordinate Jasmonate Signaling.
Jasmonates regulate plant defense and development. In Arabidopsis (Arabidopsis thaliana), JASMONATE-ASSOCIATED VQ-MOTIF GENE1 (JAV1/VQ22) is a repressor of jasmonate-mediated defense responses and is degraded through the ubiquitin-26S proteasome system after herbivory. We found that JAV1-ASSOCIATED UBIQUITIN LIGASE1 (JUL1), a RING-type E3 ubiquitin ligase, interacted with JAV1. JUL1 interacted with JAV1 in the nucleus to ubiquitinate JAV1, leading to proteasomal degradation of JAV1. The transcript levels of JUL1 and JAV1 were coordinately and positively regulated by the CORONATINE INSENSITIVE1-dependent signaling pathway in the jasmonate signaling network, but in a manner that was not dependent on CORONATINE INSENSITIVE1-mediated signaling upon herbivory by Spodoptera litura Gain or loss of function of JUL1 modulated the expression levels of the defensin gene PDF1.2 in leaves, conferring on the plants various defense properties against the generalist herbivore S. litura Because neither the JUL1 mutant nor overexpression lines showed any obvious developmental defects, we concluded that the JAV1/JUL1 system functions as a specific coordinator of reprogramming of plant defense responses. Altogether, our findings offer insight into the mechanisms by which the JAV1/JUL1 system acts specifically to coordinate plant defense responses without interfering with plant development or growth.


Trajectories of caregiver depressive symptoms while providing end-of-life care.
The course of caregivers' depressive symptoms may not be homogenous. This study identified trajectories of depressive symptoms among caregivers providing end-of-life care to cancer patients and profiled the unique characteristics of caregivers within each trajectory. Trajectories of depressive symptoms were explored in 447 caregivers who completed the Center for Epidemiological Studies Depression Scale over four periods close to the patient's death (1-30, 31-90, 91-180, and >180 days). Distinct trajectories were identified by latent class analysis. Four trajectories were identified as endurance, resilience, moderately symptomatic, and chronically distressed and contained 32.0%, 11.4%, 36.9%, and 19.7% of the sample, respectively. Caregivers in the endurance trajectory were relatively well-adjusted individuals with less education, adequate financial support, and ample psychological resources but provided care to older patients with greater symptom distress. They perceived less subjective caregiving burden than caregivers with moderate or chronic depressive symptoms. Caregivers in the resilience trajectory were in a more vulnerable position than those in other trajectories when they first transitioned into the caregiving role because they were more likely to be the patient's spouse, have greater educational attainment and insufficient finances, provide higher intensity assistance to a younger relative, and have weaker psychological resources. However, they were older, reported greater confidence in caregiving, and perceived less caregiving burden than caregivers in other trajectories. The moderately symptomatic and chronically distressed trajectories were differentiated only by the strength of psychological resources. Caregivers of terminally ill cancer patients follow distinct depressive-symptom trajectories while providing end-of-life care.


A nonlinear fractional epidemic model for the Marburg virus transmission with public health education.
In this study, a deterministic model for the dynamics of Marburg virus transmission that incorporates the impact of public health education is being formulated and analyzed. The Caputo fractional-order derivative is used to extend the traditional integer model to a fractional-based model. The model's positivity and boundedness are also under investigation. We obtain the basic reproduction number [Formula: see text] and establish the conditions for the local and global asymptotic stability for the disease-free equilibrium of the model. Under the Caputo fractional-order derivative, we establish the existence-uniqueness theory using the Banach contraction mapping principle for the solution of the proposed model. We use functional techniques to demonstrate the proposed model's stability under the Ulam-Hyers condition. The numerical solutions are being determined through the Predictor-Corrector scheme. Awareness, as a form of education that lowers the risk of danger, is reducing susceptibility and the risk of infection. We employ numerical simulations to showcase the variety of realistic parameter values that support the argument that human awareness, as a form of education, considerably lowers susceptibility and the risk of infection.


Ferromagnetic Resonance Biosensor for Homogeneous and Volumetric Detection of DNA.
The ability to detect and analyze the state of magnetic labels with high sensitivity is of crucial importance for developing magnetic biosensors. In this work, we demonstrate, for the first time, a ferromagnetic resonance (FMR) based homogeneous and volumetric biosensor for magnetic label detection. Two different isothermal amplification methods, i.e., rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP), are adopted and combined with a standard electron paramagnetic resonance (EPR) spectrometer for FMR biosensing. For the RCA-based FMR biosensor, binding of RCA products of a synthetic Vibrio cholerae target DNA sequence gives rise to the formation of aggregates of magnetic nanoparticles. Immobilization of nanoparticles within the aggregates leads to a decrease of the net anisotropy of the system and a concomitant increase of the resonance field. A limit of detection of 1 pM is obtained with a linear detection range between 7.8 and 250 pM. For the LAMP-based sensing, a synthetic Zika virus target oligonucleotide is amplified and detected in 20% serum samples. Immobilization of magnetic nanoparticles is induced by their coprecipitation with Mg2P2O7 (a byproduct of LAMP) and provides a detection sensitivity of 100 aM. The fast measurement, high sensitivity, and miniaturization potential of the proposed FMR biosensing technology makes it a promising candidate for designing future point-of-care devices.


[Study on the distribution of collagen fibers in the bifurcating area of cerebral arterioles of Wistar rats].
It was previously reported that Mato cells (Mato's fluorescent granular perithelial cells) were frequently localized in the bifurcating areas of cerebral arterioles and occasionally, collagen fibers appeared close to Mato cells of aged rats. It has also been established that Mato cells were scavenger cells in the cerebral tissue and provided with MHC-class II antigen. The present paper deals with the relationship between the distribution of collagen fibers and Mato cells in the bifurcating area of cerebral arterioles. 6 Wistar rats (3 rats aged 4 months and 3 rats aged 16 months) were employed for this electron microscopical study. They were perfused with the mixture of paraform-glutaraldehyde solution, and cerebral cortices were excised and fixed with 1% osmic solution and embedded in Epon 812. In order to observe the bifurcating area of cerebral arterioles, serial semithin sections cutting with the diamond knife were stained with toluidine blue, and checked under the light microscope. After obtaining available regions, serial thin sections were stained with uranyl acetate and lead nitrate, and observed with Hitach H7600 electron microscope. In order to survey the distribution of collagen fibers, 2 groups of the specimens of 4 months old (2 rats) and 5 groups of specimens of 16 months old rats (2 rats) were prepared. Each group consisted of serial 10 thin sections. Other rats of young and aged were used for complementary use. From the observation, it is confirmed that in the cerebral arteriole, collagen fibers are localized only in the interstices around Mato cells, and the fibers appear in a small quantity in the rats aged 4 months, while a certain amounts of the fibers are arranged sporadically in the rats aged 16 months. However, no collagen fibers can be detected in the subendothelial space and in the interstices among smooth muscle cells of cerebral arteriole. If Mato cells lack in some regions of cerebral arterioles, collagen fibers cannot be recognized. The following is also to be stressed that no fibroblastoid cells do appear in any serial sections of cerebral arterioles. From these findings, it seems possible that Mato cells play a principal role in the formation of collagen fibers in the cerebral arterioles, and associate with the sclerosis of cerebral arterioles.


Shared and Unique Disease Pathways in Amyotrophic Lateral Sclerosis and Parkinson's Disease Unveiled in Peripheral Blood Mononuclear Cells.
Recent evidence supports an association between amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Indeed, prospective population-based studies demonstrated that about one-third of ALS patients develop parkinsonian (PK) signs, even though different neuronal circuitries are involved. In this context, proteomics represents a valuable tool to identify unique and shared pathological pathways. Here, we used two-dimensional electrophoresis to obtain the proteomic profile of peripheral blood mononuclear cells (PBMCs) from PD and ALS patients including a small cohort of ALS patients with parkinsonian signs (ALS-PK). After the removal of protein spots correlating with confounding factors, we applied a sparse partial least square discriminant analysis followed by recursive feature elimination to obtain two protein classifiers able to discriminate (i) PD and ALS patients (30 spots) and (ii) ALS-PK patients among all ALS subjects (20 spots). Functionally, the glycolysis pathway was significantly overrepresented in the first signature, while extracellular interactions and intracellular signaling were enriched in the second signature. These results represent molecular evidence at the periphery for the classification of ALS-PK as ALS patients that manifest parkinsonian signs, rather than comorbid patients suffering from both ALS and PD. Moreover, we confirmed that low levels of fibrinogen in PBMCs is a characteristic feature of PD, also when compared with another movement disorder. Collectively, we provide evidence that peripheral protein signatures are a tool to differentially investigate neurodegenerative diseases and highlight altered biochemical pathways.


'The study has taught me to be supportive of her': empowering women and involving men in microbicide research.
Recognising that women often have little control over most HIV-prevention methods, including condoms, researchers have made efforts to develop new bio-technological interventions, such as microbicides, that could allow women greater autonomy in HIV-prevention decision making. In many situations, women are unable to negotiate condom use with their partners, meaning that they could be better protected through the use of an effective microbicide. This paper uses qualitative data from the Microbicide Development Programme 301 (MDP301) microbicide trial in Johannesburg, South Africa. Data is taken from in-depth interviews with male partners of female trial participants (n = 28), six focus-group discussions involving male partners of trial participants (n = 4) and female participants (n = 2). Data show that men's involvement in microbicide research ranges from a disinterest in trials to the desire to actively take part in and promote research that affects the health of themselves and their partners. Results showed that some participants were reluctant to disclose trial involvement and product use to their partners, making identifying men as potential research participants problematic. This paper considers how to involve men in microbicide research without undermining women's sense of empowerment and ownership of the trial and the product that is being tested.


DeEPn: a deep neural network based tool for enzyme functional annotation.
With the advancement of high throughput techniques, the discovery rate of enzyme sequences has increased significantly in the recent past. All of these raw sequences are required to be precisely mapped to their respective functional attributes, which helps in deciphering their biological role. In the recent past, various prediction models have been proposed to predict the enzyme functional class; however, all of these models were able to quantify at most six functional enzyme classes (EC1 to EC6) out of existing seven functional classes, making these approaches inappropriate for handling enzymes corresponding to the seventh functional class (EC7). In this study, a Deep Neural Network-based approach, DeEPn, has been proposed, which can quantify enzymes corresponding to all seven functional classes with high precision and accuracy. The proposed model was compared with two recently developed tools, ECPred and SVM-Prot. The result demonstrated that DeEPn outperformed ECPred and SVM-Prot in terms of predictive quality. The DeEPn tool has been hosted as a web-based tool at https://bioserver.iiita.ac.in/DeEPn/.Communicated by Ramaswamy H. Sarma.


Mechanism of inhibition of mitochondrial adenosine triphosphatase by dicyclohexylcarbodiimide and oligomycin: relationship to ATP synthesis.
Measurement of the rate of [gamma-32P]ATP binding (k1) and release (k-1) from catalytic sites on submitochondrial particles permitted calculation of the affinity constant in catalytic sites (k1 = K1/k1-1) of 10(12) M-1. This value is the same as that determined previously for the solubilized ATPase (F1) from beef heart mitochondria. Treatment of submitochondrial particles with dicyclohexylcarbodiimide or oligomycin so as to cause about 90% inhibition of ATPase activity was accompanied by a decrease in the binding of [gamma-32P]ATP in high-affinity catalytic sites. Under the conditions of the experiment, it is expected that the inhibitors reacted not with the ATPase itself but with other proteins in the oligomycin-sensitive ATPase complex (F0-F1). It is proposed that dicyclohexylcarbodiimide and oligomycin inhibit ATPase activity by causing a conformational change in the F0 portion of the complex that is transmitted to F1, resulting in an impaired binding of substrate in catalytic sites. These observations of apparent conformational interactions between F0 and F1 on the mitochondrial membrane are relevant to the mechanism of the coupling device that links the energy store to ATP formation in oxidative phosphorylation. It is proposed that a change in the state of ionization of one or more charged amino acid residues in F0 results in a conformational change in F0 which, transmitted to F1, reversibly alters the catalytic sites and facilitates the release of product ATP.


Polyurethanes from isosorbide-based diisocyanates.
Benign building blocks: Stereochemically pure diisocyanates were prepared on a multigram scale from succinic anhydride and isosorbide or isomannide. Characterization of polyurethanes that were produced from these diisocyanates revealed low polydispersity, high thermal stability, and stereochemistry-dependent morphology. If biobased succinic anhydride is used, then no stoichiometric petroleum-derived reagents are required in the synthesis of these materials.


[Immunotherapy in high grade astrocytomas: principles and current state].
It is generally accepted that tumour development promotes a systemic response leading to protect the host against cancer. However, tumours may as well elicit a partial immunodeficiency to avoid the development of a complete and active immune response. Since Bloom's first studies on immunotherapy to treat high grade gliomas in 1960, many attempts have been made from different medical specialties to use the immune system as a weapon against a great diversity of cancers. Main objective of this study is to outline the basic features of the immune response inside the Central Nervous System, the strategies employed by astrocytic tumours to evade body defences, and to provide an extended literature review on research on immunotherapy, especially concerning its patho-physiology and the clinical results achieved till date.


Victimization of patients with schizophrenia and related disorders.
Previous research has predominately focused on patients with mental illness as the instigators, rather than the victims, of violence and criminal activity. However, patients with schizophrenia appear to experience a higher degree of victimization compared to general community samples. We aimed to establish the 1-month prevalence of violent and non-violent victimization in a sample of patients with schizophrenia spectrum disorders and to investigate the determinants of victimization. Reports of violent and non-violent victimization were recorded in 348 patients in Dandenong, an outer metropolitan suburb of Melbourne, Australia along with the subjective perception of patients as to their degree of protection from being robbed or attacked. Patients reporting victimization were compared with those who did not, across a range of clinical and psychosocial variables. 11.2% of the sample reported being the victim of non-violent crime and 4.3% the victim of violent crime in the 1-month period. 23.2% reported dissatisfaction with their protection against being attacked or robbed. The major determinant of victimization was the lack of any meaningful daily activity. Patients with schizophrenia spectrum disorders are at increased risk of victimization, both of the violent and non-violent type. Further research is required to understand the pathways through which victimization occurs and to understand whether psychosocial interventions can reduce victimization in this patient population.


Minimum 2-Year Analysis of S2-Alar-Iliac Screw Fixation for Adult Spinal Deformity.
Retrospective cohort. Determine the rate and risk factors for S2AI screw-related pain after adult spinal deformity surgery with a minimum 2-year follow-up. A consecutive 83 spinal deformity patients undergoing surgical treatment between August 2015 and December 2017 with minimum 2-year follow-up for S2AI screw complication and screw-related pain were included. Linear regression was performed on various risk factors and postoperative S2AI screw-related pain. Subset analysis of 53 patients was performed on preoperative and postoperative SRS and ODI scores, operative data, and radiographic data. The overall proportion of S2AI screw-related pain was 9.6%. An S2AI screw complication was identified radiographically in 10.8% of patients; among these, 22.2% experienced S2AI screw-related pain. 3.4% of all patients underwent S2A1 screw removal. The SRS, ODI, sagittal vertical axis (SVA), and coronal alignment scores/measurements improved following treatment in all patients. However, the mean difference for the pre and postoperative SRS function score (1.2 ± 0.5 vs 0.9 ± 0.8) and SVA (4.0 ± 4.9 cm vs 2.1 ± 4.8 cm) were higher for the pain group. A minimum 2-year analysis of S2AI screw fixation in adult spinal deformity patients showed that 9.6% of patients experienced S2AI screw-related pain and 3.4% of patients had S2A1 screws removed. The size and the number of S2AI screws did not predict postoperative pain, nor were radiographic findings correlated with clinical outcomes. The patient outcome scores, coronal alignment, and SVA improved for all patients, but within the pain group there was an overall larger change in the SVA and SRS function score.


Stages of Behavior Change for Physical Activity in Airport Staff: a quasi-experimental study.
This work sought to determine the effect of an educational intervention based on the stages of change in promoting physical activity in employees in the Mashhad airport in Iran. This was a quasi-experimental study conducted with the participation of 60 volunteers (30 in the intervention group and 30 in the control group) who were in the stages of contemplating or preparing for change in physical activity. The intervention consisted in educational activities provided during home visits, telephone calls, group training sessions, and delivery of printed material. To gather the information, the study used five questions on the stage in which they were for behavioral change in physical activity, according to the Theoretical Model by Marcus et al., (1. pre-contemplation, 2. contemplation, 3. preparation, 4. action, and 5. maintenance), and the International Questionnaire on Physical Activity. Changes in the stages were evaluated during three moments: upon entering the study, at the end of the intervention (8th month), and two months after the second evaluation (10th month). During the 10th month evaluation, it was noted that 26.7% of the subjects from the intervention group versus 3.3% from the control group improved their physical activity and were in the action stage (p < 0.01). The educational intervention based on stages of change is effective in promoting physical activity in the participants and may be used in educational programs that seek to improve physical activity in the employees studied.


Development of Neutropenic Murine Models of Iron Overload and Depletion To Study the Efficacy of Siderophore-Antibiotic Conjugates.
Siderophore-antibiotic conjugates have increased in vitro activity in low-iron environments where bacteria express siderophores and associated transporters. The host immune hypoferremic response reduces iron availability to bacteria; however, patients with iron overload or deficiency may have altered ability to restrict iron, which may affect the efficacy of siderophore-antibiotic conjugates. In vivo models of infection with iron overload and deficiency are needed to perform this assessment. The standard neutropenic murine thigh infection model was supplemented with iron-altering treatments: iron dextran at 100 mg/kg of body weight daily for 14 days to load iron or deferoxamine at 100 mg/kg daily plus a low-iron diet for up to 30 days to deplete iron. Human-simulated regimens of cefiderocol and meropenem were administered in both models to assess any impact of iron alteration on plasma pharmacokinetics. Median iron in overloaded mice was significantly higher than that of controls in plasma (1,657 versus 336 μg/dl; P < 0.001), liver (2,133 versus 11 μg/g; P < 0.001), and spleen (473 versus 144 μg/g; P < 0.001). At 30 days, depleted mice had significantly lower iron than controls in liver (2.4 versus 6.5 μg/g; P < 0.001) and spleen (72 versus 133 μg/g; P = 0.029) but not plasma (351 versus 324 μg/dl; P = 0.95). Cefiderocol and meropenem plasma concentrations were similar in iron overloaded and control mice but varied in iron-depleted mice. The iron-overloaded murine thigh infection model was established, and human-simulated regimens of cefiderocol and meropenem were validated therein. While deferoxamine successfully reduced liver and splenic iron, this depleting treatment altered the pharmacokinetics of both antimicrobials.


[Effect of a long-term cholesterol-rich diet on the serum and hepatic lipid and lipoprotein levels in normotensive and spontaneously hypertensive rats].
There are great species and individual differences in response of the organism to a diet, rich in cholesterol. In the present study the author used two types of rats-normotonic of Wistar strain and spontaneously hypertonic of Okamoto--Aoki strain. The animals were fed with a diet of O'Neil, rich in cholesterol, for various periods of time. The levels of liver lipids and serum lipoproteins were raised only in the normotonic Wistar rats at early periods (4 months). The levels of serum lipids were elevated only after 10- and 11-month feeding with a diet, rich in cholesterol. She discusses the possibility that the increased exogenic transport of cholesterol and lipids could be compensated by enhanced metabolism in the peripheral tissues and by suppression and catabolism of cholesterol in liver at earlier stages. She suggests that the early elevation of lipoproteins could be due to "intermediary" lipoproteins, rich in cholesterol. This is proven also by the disc electrophoresis of serum lipoproteins, revealing intensification of alpha-lipoprotein fraction and the intermediary fraction between beta-lipoproteins and pre-beta-lipoproteins. There is no humoral syndrome, observed in the normotonic Wistar rats, in the spontaneously hypertonic rats, which have a--6-month diet, although the levels of liver lipids are raised significantly, when they are compared with the control group. She discusses the possibility for greater centrifugal transport of this kind, since more cholesterol and lipoproteins are measured in the vascular wall than in the normotonic animals.


Are unpaired chromosomes spermicidal?: A maximum-likelihood analysis of segregation and meiotic drive in Drosophila melanogaster males deficient for the ribosomal-dna.
Meiosis in Drosophila melanogaster males is achiasmate and requires special systems to ensure normal segregation. Several situations that yield frequent nondisjunction also produce high levels of chromatin-dependent sperm lethality, suggesting the possibility of a simple and direct connection between defective disjunction and defective sperm development. One hypothesis that has been offered is that pairing not only ensures disjunction, but also changes the physical state of chromosomes so that they can be packaged in sperm. Here, I present an analysis of extensive data on disjunction and sperm survival in rDNA-deficient males collected by B. McKee and D. Lindsley. This analysis demonstrates that, although nondisjunction and sperm lethality are indeed correlated, the basis of this is not the presence of unpaired chromosomes in the sperm. Chromosomes that have failed to disjoin are not themselves spermicidal.


Enhancing dermatology nursing education in Scotland and Ireland: a multifaceted approach.
The purpose of the National Dermatology Improvement Project was to identify the educational requirements of dermatology nurses and understand factors impacting the uptake of education for nurses. An educational needs analysis was performed to evaluate the strengths and weaknesses of current and future educational provision for all levels of nursing staff. Data were collected from department managers using questionnaires and interviews, and focus groups were held with nursing staff in bands 2-7. The majority of participants felt there was an overall lack of dermatology education, and that most of what was available was peer led and experiential. A number of barriers to the uptake of education were also identified, such as a lack of time, opportunity and motivation. These findings support the need for a nationally coordinated programme of dermatology education with formal and informal education provided for all levels of dermatology nursing staff.


Steatorrhea and pancreatic insufficiency in Shwachman syndrome.
Fat absorption was assessed on two or more occasions in 12 of 14 patients with Shwachman syndrome. Of 11 children who initially had steatorrhea, 6 were subsequently found to have normal fat excretion. In 10 of these 11 patients the last estimate was smaller than the initial estimate after an interval of 0.3-12.7 yr. The most dramatic improvement occurred under 4 yr of age but improvement appeared to continue over a more extended period where sufficient follow-up was available. All patients had pronounced pancreatic insufficiency as tested by duodenal drainage corrected by nonabsorbable marker under stimulation with cholecystokinin and secretin. Pancreatic lipase secretion was assessed in 3 patients with steatorrhea and 5 without steatorrhea (73% of the surviving patients) using a sensitive assay which used maximum stimulation with colipase. Pancreatic lipase secretion was less than 2% of normal mean secretion in the steatorrheic patients and ranged from 3.7% to 13.6% in the patients without steatorrhea. These results indicate that fat absorption improves in the majority of patients with Shwachman syndrome and appears to be associated with marginal improvement in pancreatic lipase secretion. Due to the occult nature of bowel complaints in older patients, the diagnosis may be overlooked unless careful screening for pancreatic function takes place.


Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial.
To determine the effects of myo-inositol on oocyte quality in polycystic ovary syndrome (PCOS) patients undergoing intracytoplasmic sperm injection (ICSI) cycles. A prospective, controlled, randomized trial. Assisted reproduction centers. Sixty infertile PCO patients undergoing ovulation induction for ICSI. All participants underwent standard long protocol. Starting on the day of GnRH administration, 30 participants received myo-inositol combined with folic acid (Inofolic) 2 g twice a day and 30 control women received folic acid alone, administrated continuously. Primary end points were number of morphologically mature oocytes retrieved, embryo quality, and pregnancy and implantation rates. Secondary end points were total number of days of FSH stimulation, total dose of gonadotropin administered, E(2) level on the day of hCG administration, fertilization rate per number of retrieved oocytes, embryo cleavage rate, live birth and miscarriage rates, cancellation rate, and incidence of moderate or severe ovarian hyperstimulation syndrome. Total r-FSH units (1,958 +/- 695 vs. 2,383 +/- 578) and number of days of stimulation (11.4 +/- 0.9 vs. 12.4 +/- 1.4) were significantly reduced in the myo-inositol group. Furthermore, peak E(2) levels (2,232 +/- 510 vs. 2,713 +/- 595 pg/mL) at hCG administration were significantly lower in patients receiving myo-inositol. The mean number of oocytes retrieved did not differ in the two groups, whereas in the group cotreated with myo-inositol the mean number of germinal vesicles and degenerated oocytes was significantly reduced (1.0 +/- 0.9 vs. 1.6 +/- 1.0), with a trend for increased percentage of oocytes in metaphase II (0.82 +/- 0.11% vs. 0.75 +/- 0.15%). These data show that in patients with PCOS, treatment with myo-inositol and folic acid, but not folic acid alone, reduces germinal vesicles and degenerated oocytes at ovum pick-up without compromising total number of retrieved oocytes. This approach, reducing E(2) levels at hGC administration, could be adopted to decrease the risk of hyperstimulation in such patients.


Quantitative detection of Borrelia burgdorferi with a microtiter-based competitive polymerase chain reaction assay.
The current understanding of the inflammation associated with Lyme disease directly involves infection caused by Borrelia burgdorferi within specific target tissues, accompanied by a significant host immunologic component driving the inflammatory process. The measurement of spirochetal tissue burden may thus be useful for studying animal models of Lyme disease pathogenesis. Widely available methods based on the culture of spirochetes from tissues do not provide quantitative information. We developed and evaluated a quantitative-competitive polymerase chain reaction assay based on amplification of the B. burgdorferi flagellin gene. The assay makes use of a competitive internal standard and a commercially available enzyme-linked immunosorbent assay detection kit. The assay clearly discriminated between infected and uninfected mouse tissues, and an accurate quantitation range of 500 to 20,000 spirochetes per milligram of tissue was obtained. C3H mice were shown to harbor greater amounts of spirochetal genomic DNA than BALB/c mice. Normalization of samples by tissue weight and genomic DNA content both provided acceptable results. These data indicate this assay can be used to provide reliable and meaningful measurements of spirochetal infectious burden, which will be extremely useful for the study of Lyme disease pathogenesis in the murine model.


Quality Assessment of the Chinese Clinical Trial Protocols Regarding Treatments for Coronavirus Disease 2019.
With the global spread of coronavirus disease 2019 (COVID-19), an increasing number of clinical trials are being designed and executed to evaluate the efficacy and safety of various therapies for COVID-19. We conducted this survey to assess the methodological quality of registry protocols on potential treatments for COVID-19. Clinical trial protocols were identified on the ClinicalTrials.gov and the Chinese Clinical Trial Registry. Protocols were screened by two investigators independently against pre-defined eligibility criteria. Quality of the included protocols was assessed according to the modified 14-item SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement. We included 82 randomized controlled trial (RCT) protocols investigating treatment modalities for COVID-19. These ongoing trials are being conducted in 16 provinces, autonomous regions, and municipalities of China, and study interventions were either Western medicines (n = 56) or traditional Chinese medicine (n = 26). Findings of our quality assessment indicated that the existing trial protocols could be further improved on several aspects, including selection and definition of outcome measures, descriptions of study interventions and comparators, study subject recruitment time, definition of study inclusion and exclusion criteria, and allocation concealment methods. Descriptions of random sequence generation methodologies were accurate for the majority of included trial protocols (n = 64; 78.05%); however, reporting of allocation concealment remained unclear in 63 (76.83%) protocols. Therefore, the overall risk of selection bias across these RCTs was judged to be unclear. A total of 52 (63.41%) included RCT protocols were open-label trials and are thus associated with a high risk of performance bias and detection bias. Quality of currently available RCT protocols on the treatments for COVID-19 could be further improved. For transparency and effective knowledge translation in real-world clinically settings, it is important for trial investigators to standardize baseline treatments for patients with COVID-19 and assess clinically important core outcome measures. Despite eager anticipation from the public on the results of effectiveness trials in COVID-19, robust design, execution, and reporting of these trials should be regarded as high priority.


Evaluation of the An-Ident system and an indole spot test for the rapid differentiation of porcine treponemes.
The An-Ident strip system (Analytab Products Inc., St-Laurent, Quebec, Canada) was evaluated for its ability to differentiate Treponema hyodysenteriae from Treponema innocens. Of the 20 tests included on this strip, 15 yielded identical results for the two species. Among the other five assays, none could be considered as a positive discriminator for the two species. However, when an indole spot test with 1% p-dimethylaminocinnamaldehyde was used in parallel, all reference strains and 97% of the isolates of T. hyodysenteriae were positive, whereas all isolates of T. innocens were negative. Our results indicate that An-Indent is of little value for the differentiation of the two species. Our results also suggest that a rapid and simple differentiation between T. hyodysenteriae and T. innocens can be achieved by using the hemolysis and ring phenomenon tests in conjunction with an indole spot test.


Druggability analysis and structural classification of bromodomain acetyl-lysine binding sites.
Bromodomains are readers of the epigenetic code that specifically bind acetyl-lysine containing recognition sites on proteins. Recently the BET family of bromodomains has been demonstrated to be druggable through the discovery of potent inhibitors, sparking an interest in protein-protein interaction inhibitors that directly target gene transcription. Here, we assess the druggability of diverse members of the bromodomain family using SiteMap and show that there are significant differences in predicted druggability. Furthermore, we trace these differences in druggability back to unique amino acid signatures in the bromodomain acetyl-lysine binding sites. These signatures were then used to generate a new classification of the bromodomain family, visualized as a classification tree. This represents the first analysis of this type for the bromodomain family and can prove useful in the discovery of inhibitors, particularly for anticipating screening hit rates, identifying inhibitors that can be explored for lead hopping approaches, and selecting proteins for selectivity screening.


Response surface modeling of boron adsorption from aqueous solution by vermiculite using different adsorption agents: Box-Behnken experimental design.
In this study, a different method was applied for boron removal by using vermiculite as the adsorbent. Vermiculite, which was used in the experiments, was not modified with adsorption agents before boron adsorption using a separate process. Hexadecyltrimethylammonium bromide (HDTMA) and Gallic acid (GA) were used as adsorption agents for vermiculite by maintaining the solid/liquid ratio at 12.5 g/L. HDTMA/GA concentration, contact time, pH, initial boron concentration, inert electrolyte and temperature effects on boron adsorption were analyzed. A three-factor, three-level Box-Behnken design model combined with response surface method (RSM) was employed to examine and optimize process variables for boron adsorption from aqueous solution by vermiculite using HDTMA and GA. Solution pH (2-12), temperature (25-60 °C) and initial boron concentration (50-8,000 mg/L) were chosen as independent variables and coded x1, x2 and x3 at three levels (-1, 0 and 1). Analysis of variance was used to test the significance of variables and their interactions with 95% confidence limit (α = 0.05). According to the regression coefficients, a second-order empirical equation was evaluated between the adsorption capacity (qi) and the coded variables tested (xi). Optimum values of the variables were also evaluated for maximum boron adsorption by vermiculite-HDTMA (HDTMA-Verm) and vermiculite-GA (GA-Verm).


Surgical treatment of distal biceps rupture.
Rupture of the distal biceps tendon accounts for 10% of all biceps brachii ruptures. Injuries typically occur in the dominant elbow of men aged 40 to 49 years during eccentric contraction of the biceps. Degenerative changes, decreased vascularity, and tendon impingement may precede rupture. Although nonsurgical management is an option, healthy, active persons with distal biceps tendon ruptures benefit from early surgical repair, gaining improved strength in forearm supination and, to a lesser degree, elbow flexion. Biomechanical studies have tested the strength and displacement of various repairs; the suspensory cortical button technique exhibits maximum peak load to failure in vitro, and suture anchor and interosseous screw techniques yield the least displacement. Surgical complications include sensory and motor neurapraxia, infection, and heterotopic ossification. Current trends in postoperative rehabilitation include an early return to motion and to activities of daily living.


ADRF Trebitsch Scholarship. The microbial contamination of toothbrushes. A pilot study.
Ten individuals were each supplied with a new toothbrush of the same type and brand, together with identical tubes of fluoridated toothpaste. After a three-week period, during which subjects were asked to follow their usual oral hygiene practices, the toothbrushes were collected and assayed for microbial contamination using a range of selective growth media. The total microbial load per toothbrush was found to be 10(4) to 10(5) colony forming units. Staphylococci were found on all toothbrushes and streptococci on all but one. These two genera were also quantitatively dominant. Candida, corynebacteria, pseudomonads and coliforms were identified in 70, 60, 50 and 30 per cent of toothbrushes, respectively. However, mutans streptococci, lactobacilli and black-pigmented Gram-negative anaerobic rods were not detected on any of the toothbrushes. For each individual, information on variables such as toothbrush rinsing practices and post-brushing storage methods and environment was collected. No obvious relationship between such variables and microbial load was apparent but it is suggested that more extensive studies are needed, taking into account additional parameters such as age and degree of toothbrush wear and the use of pre-brushing mouthwashes.


The use and abuse of aesthetic materials in posterior teeth.
This paper summarizes the clinically significant concerns surrounding the use of aesthetic restoratives in posterior teeth. Composite resins are far from ideal and possess some properties that should be of real concern to the dentist. They are not amalgam substitutes. On the other hand, they do have a place in the conservative cavity where aesthetics are desired. The suggested use of composite and porcelain inlays or onlays is an attempt to circumvent some of the concerns generated by the routine use of composites. However, the relative scarcity of clinical studies suggests a limited usage at this time.


Evolutionary history of the parrotfishes: biogeography, ecomorphology, and comparative diversity.
The family Scaridae comprises about 90 species of herbivorous coral reef, rock reef, and seagrass fishes. Parrotfishes are important agents of marine bioerosion who rework the substrate with their beaklike oral jaws. Many scarid populations are characterized by complex social systems including highly differentiated sexual stages, territoriality, and the defense of harems. Here, we test a hypothesis of relationships among parrotfish genera derived from nearly 2 kb of nuclear and mitochondrial DNA sequence. The DNA tree is different than a phylogeny based on comparative morphology and leads to important reinterpretations of scarid evolution. The molecular data suggest a split among seagrass and coral reef associated genera with nearly 80% of all species in the coral reef clade. Our phylogenetic results imply an East Tethyan origin of the family and the recurrent evolution of excavating and scraping feeding modes. It is likely that ecomorphological differences played a significant role in the initial divergence of major scarid lineages, but that variation in color and breeding behavior has triggered subsequent diversification. We present a two-phase model of parrotfish evolution to explain patterns of comparative diversity. Finally, we discuss the application of this model to other adaptively radiating clades.


Treatment of Pseudomonas aeruginosa infections with pyocines.
The interactions of a contractile, a filamentous and a small pyocine with a sensitive strain of Pseudomonas aeruginosa (no. P14) were examined in vivo. The purification procedure used yielded high-activity pyocine preparations that were not toxic to mice. The inhibitory activity of such preparations, when injected into mice by various routes, was retained for up to 24 h. However, high molecular-weight pyocines given intraperitoneally in the presence of a lethal dose of strain P14 administered by the same route did not prevent the fatal outcome of infection unless they are given before or together with the bacteria. The small pyocine had no protective effect. In burned mice infected with strain P14, topical application of a filamentous pyocine failed to improve the chances of survival. The results suggest that there is little future for pyocine therapy.


Recurrence after total thyroidectomy for benign multinodular goiter.
Total thyroidectomy is now the preferred option for the management of benign multinodular goiter (BMNG), and it ought not be associated with recurrent disease. The aim of the present study was to examine the efficacy of total thyroidectomy for BMNG and to review reasons for recurrence. The study group comprised all patients from January 1980 to December 2005 who underwent a definitive procedure to remove all thyroid tissue for BMNG, and who were subsequently identified as having developed a recurrence. Included were patients who underwent primary total thyroidectomy at our unit, or a two or more stage procedure where a definitive secondary total thyroidectomy was performed at our unit. There were 3,044 total or secondary total thyroidectomies performed for BMNG during the study period. Ten patients were identified as having developed recurrent BMNG requiring reoperation despite previous complete "total" thyroidectomy. There were 11 sites of recurrence in 10 patients. Only one was a true local recurrence in the thyroid bed. Another 9 recurrences related to the embryology of the thyroid gland, 4 in the pyramidal tract and 5 in the thyrothymic tract. There was one recurrence at another site (submandibular) in a patient with presumed metastatic thyroid cancer despite benign histology. There were no complications in any of the 10 patients. Total thyroidectomy for BMNG is not only a safe procedure but is efficacious in preventing recurrent disease. Failure to remove embryological remnants such as thyrothymic residue or pyramidal remnants during total thyroidectomy is the major cause of recurrence.


Active commuting and sociodemographic factors among university students in Spain.
Commuting to university represents an opportunity to incorporate physical activity (walking or biking) into students' daily routines. There are few studies that analyze patterns of transport in university populations. This cross-sectional study estimated energy expenditure from active commuting to university (ACU) and examined sociodemographic differences in findings. The sample included 518 students with a mean age of 22.4 years (59.7% female) from 2 urban universities in Valencia, Spain. Time spent in each mode of transport to university and sociodemographic factors was assessed by self-report. Nearly 35% of the students reported walking or biking as their main mode of transport. ACU (min/wk) were highest for walkers (168) and cyclists (137) and lowest for motorbike riders (0.0) and car drivers (16). Public transport users, younger students, low socioeconomic status students, and those living ≤ 2 km from the university had higher energy expenditure from active commuting than comparison groups. Biking was highest among those living 2-5 km from the university. Our findings suggest that active commuting and public transit use generated substantial weekly energy expenditure, contributed to meeting physical activity recommendations, and may aid in obesity prevention.


The decline and fate of an iron-induced subarctic phytoplankton bloom.
Iron supply has a key role in stimulating phytoplankton blooms in high-nitrate low-chlorophyll oceanic waters. However, the fate of the carbon fixed by these blooms, and how efficiently it is exported into the ocean's interior, remains largely unknown. Here we report on the decline and fate of an iron-stimulated diatom bloom in the Gulf of Alaska. The bloom terminated on day 18, following the depletion of iron and then silicic acid, after which mixed-layer particulate organic carbon (POC) concentrations declined over six days. Increased particulate silica export via sinking diatoms was recorded in sediment traps at depths between 50 and 125 m from day 21, yet increased POC export was not evident until day 24. Only a small proportion of the mixed-layer POC was intercepted by the traps, with more than half of the mixed-layer POC deficit attributable to bacterial remineralization and mesozooplankton grazing. The depletion of silicic acid and the inefficient transfer of iron-increased POC below the permanent thermocline have major implications both for the biogeochemical interpretation of times of greater iron supply in the geological past, and also for proposed geo-engineering schemes to increase oceanic carbon sequestration.


A molecular simulation probing of structure and interaction for supramolecular sodium dodecyl sulfate/single-wall carbon nanotube assemblies.
Here we report a larger-scale atomic-level molecular dynamics (MD) simulation for the self-assembly of sodium dodecyl sulfate (SDS) surfactant on single-walled carbon nanotube (SWNT) surfaces and the interaction between supramolecular SDS/SWNT aggregates. We make an effort to address several important problems in regard to carbon nanotube dispersion/separation. At first, the simulation provides comprehensive direct evidence for SDS self-assembly structures on carbon nanotube surfaces, which can help to clarify the relevant debate over the exact adsorption structure. We also, for the first time, simulated the potential of mean force (PMF) between two SWNTs embedded in SDS surfactant micelles. A novel unified PMF approach has been applied to reveal various cooperative interactions between the SDS/SWNT aggregates, which is different from the previous electrostatic repulsion explanation. The unique role of sodium ions revealed here provides a new microscopic understanding of the recent experiments in the electrolyte tuning of the interfacial forces on the selective fractionation of SDS surrounding SWNTs.


Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial.
In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, bivalirudin with provisional glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition was found to be noninferior to heparin plus planned Gp IIb/IIIa blockade in the prevention of acute ischemic end points and was associated with significantly less bleeding by 30 days after percutaneous coronary intervention (PCI). To determine whether the efficacy of bivalirudin remains comparable with that of heparin plus Gp IIb/IIIa blockade over 6 months and 1 year. Follow-up study to 1 year of a randomized, double-blind trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002. Patients were randomly assigned to receive intravenously bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition, or to receive heparin (65 U/kg bolus), with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI. Incidence of death, myocardial infarction, or repeat revascularization by 6 months and death by 12 months after enrollment. At 6 months, death occurred in 1.4% of patients in the heparin plus Gp IIb/IIIa group and in 1.0% of patients in the bivalirudin group (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.43-1.14; P =.15). Myocardial infarction occurred in 7.4% and 8.2% of patients, respectively (HR, 1.12; 95% CI, 0.93-1.34; P =.24), and repeat revascularization was required in 11.4% and 12.1% of patients, respectively (HR, 1.06; 95% CI, 0.91-1.23; P =.45). By 1 year, death occurred in 2.46% of patients treated with heparin plus Gp IIb/IIIa blockade and in 1.89% of patients treated with bivalirudin (HR, 0.78; 95% CI, 0.55-1.11; P =.16). Nonsignificant trends toward lower 1-year mortality with bivalirudin were present in all patient subgroups analyzed and were of greatest magnitude among high-risk patients. Long-term clinical outcome with bivalirudin and provisional Gp IIb/IIIa blockade is comparable with that of heparin plus planned Gp IIb/IIIa inhibition during contemporary PCI.


Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study.
Despite great progress in curing childhood acute lymphoblastic leukemia (ALL), survival after relapse remains poor. We analyzed survival after relapse among 9585 pediatric patients enrolled on Children's Oncology Group clinical trials between 1988 and 2002. A total of 1961 patients (20.5%) experienced relapse at any site. The primary end point was survival. Patients were subcategorized by the site of relapse and timing of relapse from initial diagnosis. Time to relapse remains the strongest predictor of survival. Patients experiencing early relapse less than 18 months from initial diagnosis had a particularly poor outcome with a 5-year survival estimate of 21.0+/-1.8%. Standard risk patients who relapsed had improved survival compared with their higher risk counterparts; differences in survival for the two risk groups was most pronounced for patients relapsing after 18 months. Adjusting for both time and relapse site, multivariate analysis showed that age (10+ years) and the presence of central nervous system disease at diagnosis, male gender, and T-cell disease were significant predictors of inferior post-relapse survival. It can be noted that there was no difference in survival rates for relapsed patients in earlier vs later era trials. New therapeutic strategies are urgently needed for children with relapsed ALL and efforts should focus on discovering the biological pathways that mediate drug resistance.


Ultrabroadband 2D electronic spectroscopy with high-speed, shot-to-shot detection.
Two-dimensional electronic spectroscopy (2DES) is an incisive tool for disentangling excited state energies and dynamics in the condensed phase by directly mapping out the correlation between excitation and emission frequencies as a function of time. Despite its enhanced frequency resolution, the spectral window of detection is limited to the laser bandwidth, which has often hindered the visualization of full electronic energy relaxation pathways spread over the entire visible region. Here, we describe a high-sensitivity, ultrabroadband 2DES apparatus. We report a new combination of a simple and robust setup for increased spectral bandwidth and shot-to-shot detection. We utilize 8-fs supercontinuum pulses generated by gas filamentation spanning the entire visible region (450 - 800 nm), which allows for a simultaneous interrogation of electronic transitions over a 200-nm bandwidth, and an all-reflective interferometric delay system with angled nanopositioner stages achieves interferometric precision in coherence time control without introducing wavelength-dependent dispersion to the ultrabroadband spectrum. To address deterioration of detection sensitivity due to the inherent instability of ultrabroadband sources, we introduce a 5-kHz shot-to-shot, dual chopping acquisition scheme by combining a high-speed line-scan camera and two optical choppers to remove scatter contributions from the signal. Comparison of 2D spectra acquired by shot-to-shot detection and averaged detection shows a 15-fold improvement in the signal-to-noise ratio. This is the first direct quantification of detection sensitivity on a filamentation-based ultrabroadband 2DES apparatus.


Hydration state controls stress responsiveness and social behavior.
Life stress frequently occurs within the context of homeostatic challenge, requiring integration of physiological and psychological need into appropriate hormonal, cardiovascular, and behavioral responses. To test neural mechanisms underlying stress integration within the context of homeostatic adversity, we evaluated the impact of a pronounced physiological (hypernatremia) challenge on hypothalamic-pituitary-adrenal (HPA), cardiovascular, and behavioral responses to an acute psychogenic stress. Relative to normonatremic controls, rats rendered mildly hypernatremic had decreased HPA activation in response to physical restraint, a commonly used rodent model of psychogenic stress. In addition, acute hypernatremia attenuated the cardiovascular response to restraint and promoted faster recovery to prestress levels. Subsequent to restraint, hypernatremic rats had significantly more c-Fos expression in oxytocin- and vasopressin-containing neurons within the supraoptic and paraventricular nuclei of the hypothalamus. Hypernatremia also completely eliminated the increased plasma renin activity that accompanied restraint in controls, but greatly elevated circulating levels of oxytocin. The endocrine and cardiovascular profile of hypernatremic rats was predictive of decreased anxiety-like behavior in the social interaction test. Collectively, the results indicate that acute hypernatremia is a potent inhibitor of the HPA, cardiovascular, and behavioral limbs of the stress response. The implications are that the compensatory responses that promote renal-sodium excretion when faced with hypernatremia also act on the nervous system to decrease reactivity to psychogenic stressors and facilitate social behavior, which may suppress the anxiety associated with approaching a communal water source and support the social interactions that may be encountered when engaging in drinking behavior.


Na-K pump current in the Amphiuma collecting tubule.
There is strong evidence supporting the hypothesis of an electrogenic Na-K pump in the basolateral membrane of several epithelia. Thermodynamic considerations and results in nonepithelial cells indicate that the current carried by the pump could be voltage dependent. In order to measure the pump current and to determine its voltage dependence in a tight epithelium, we have used the isolated perfused collecting tubule of Amphiuma and developed a technique for clamping the basolateral membrane potential (Vbl) through transepithelial current injection. The transcellular current was calculated by subtracting the paracellular current (calculated from the transepithelial conductance measured in the presence of luminal amiloride) from the total transepithelial current. Basolateral membrane current-voltage (I-V) curves were obtained in conditions where the ratio of the pump current to the total basolateral membrane current had been maximized by loading the cells with Na+ (exposure to low-K+ bath), and by blocking the basolateral K+ conductance with barium. The pump current was defined as the difference of the current across the basolateral membrane measured before and 10-15 s after the addition of strophanthidin (20 microM) to the bath solution. With a bath solution containing 3 mM K+, the pump current was nearly constant in the Vbl range of -20 to -80 mV (52 +/- 5 microA.cm-2 at -60 mV) but showed a marked voltage dependence at higher negative Vbl (pump current decreased to 5 +/- 9 microA.cm-2 at -180 mV). In a 1.0 mM K bath, the shape of the pump I-V curve was similar but the amplitude of the current was decreased (24 +/- 4 microA.cm-2 at -60 mV). In a 0.1 mM K bath, the pump current was not significantly different from 0. Our results indicate that the basolateral Na-K pump generates a current which depends on the extracellular potassium concentration. With physiological peritubular concentration of K+ and in the physiological range of potential, the pump activity, measured as the pump-generated current, was independent of the membrane potential.


Uncertainty about predation risk: a conceptual review.
Uncertainty has long been of interest to economists and psychologists and has more recently gained attention among ecologists. In the ecological world, animals must regularly make decisions related to finding resources and avoiding threats. Here, we describe uncertainty as a perceptual phenomenon of decision-makers, and we focus specifically on the functional ecology of such uncertainty regarding predation risk. Like all uncertainty, uncertainty about predation risk reflects informational limitations. When cues are available, they may be novel (i.e. unknown information), incomplete, unreliable, overly abundant and complex, or conflicting. We review recent studies that have used these informational limitations to induce uncertainty of predation risk. These studies have typically used either over-responses to novelty (i.e. neophobia) or memory attenuation as proxies for measuring uncertainty. Because changes in the environment, particularly unpredictable changes, drive informational limitations, we describe studies assessing unpredictable variance in spatio-temporal predation risk, intensity of predation risk, predator encounter rate, and predator diversity. We also highlight anthropogenic changes within habitats that are likely to have dramatic impacts on information availability and thus uncertainty in antipredator decisions in the modern world.


Neuroendoscopic hematoma removal with a small craniotomy for acute subdural hematoma.
The present study evaluated the safety and effectiveness of neuroendoscopic hematoma removal with a small craniotomy for the treatment of acute subdural hematoma (ASDH). Five patients (4 men and 1 woman) with ASDH underwent neuroendoscopic surgery with a small-size craniotomy between October 2016 and June 2018. The mean age was 87.4 years (range, 82-94). The eligibility criteria were as follows: 1) the presence of symptoms; 2) no moderate or massive brain contusion or edema; and 3) inability to use a large craniotomy because of poor general condition or absence of an anesthesiologist. After performing the small craniotomy, a 4-mm rigid endoscope was inserted and the hematoma was evacuated. Endoscopic surgery was performed under general or local anesthesia. The bleeding origin was a cortical artery in 2 cases, a bridging vein in 2 cases, and unknown in 1 case. The hematoma was completely removed without re-bleeding and the procedure was lifesaving in all cases. Three patients were discharged with independent gait following rehabilitation whereas 2 patients died due to causes unrelated to ASDH. Despite some surgical limitations, neuroendoscopic hematoma evacuation of ASDH is a safe and effective method that minimizes operative complications in some cases. Small craniotomy was sufficient for inserting and maneuvering ordinal neurosurgical instruments. This technique should be considered carefully before surgery in cases of ASDH.


A new approach to estimating the prevalence of hereditary hearing loss: An analysis of the distribution of sign language users based on census data in Russia.
The absence of comparable epidemiological data challenges the correct estimation of the prevalence of congenital hearing loss (HL) around the world. Sign language (SL) is known as the main type of communication of deaf people. We suggest that the distribution of SL can be interpreted as an indirect indicator of the prevalence of congenital HL. Since a significant part of congenital HL is due to genetic causes, an assessment of the distribution of SL users can reveal regions with an extensive accumulation of hereditary HL. For the first time, we analyzed the data on the distribution of SL users that became available for the total population of Russia by the 2010 census. Seventy-three out of 85 federal regions of Russia were ranked into three groups by the 25th and 75th percentiles of the proportion of SL users: 14 regions-"low proportion"; 48 regions-"average proportion"; and 11 regions-"high proportion". We consider that the observed uneven prevalence of SL users can reflect underlying hereditary forms of congenital HL accumulated in certain populations by specific genetic background and population structure. At least, the data from this study indicate that the highest proportions of SL users detected in some Siberian regions are consistent with the reported accumulation of specific hereditary HL forms in indigenous Yakut, Tuvinian and Altaian populations.


Syncope and driving, flying and vocational concerns.
When advising a syncope patient about resumption of driving, flying or vocational activities, physicians must consider relevant laws and regulations, the etiology of the syncope, and the risk of recurrence and the impact of recurrence on the safety of the patient and others. Guidelines from professional cardiology societies may aid the physician. In the United States, private driving is regulated by individual states and their laws show significant variance. Commercial driving and flying are regulated at the federal level. These regulations tend to be more uniform, but are significantly stricter due to the potential risk to the public posed by commercial drivers or pilots with syncope. For many diagnoses, both regulations and professional society recommendations incorporate an observation period following the index syncopal event. This is due to the natural history of syncope recurrence and to allow time to monitor the response to treatment.


pH-Sensitive surfactants from lysine: assessment of their cytotoxicity and environmental behavior.
The toxicity and environmental behavior of new pH-sensitive surfactants from lysine are presented. Three different chemical structures are studied: surfactants with one amino acid and one alkyl chain, surfactants with two amino acids on the polar head and one alkyl chain, and gemini surfactants. The pH sensitivity of these compounds can be tuned by modifying their chemical structures. Cytotoxicity has been evaluated using erythrocytes and fibroblast cells. The toxic effects against these cells depend on the hydrophobicity of the molecules as well as their cationic charge density. The effect of hydrophobicity and cationic charge density on toxicity is different for each type of cells. For erythrocytes, the toxicity increases as hydrophobicity and charge density increases. Nevertheless, for fibroblasts cationic charge density affects cytotoxicity in the opposite way: the higher charge density, the lower the toxicity. The effect of the pH on hemolysis has been evaluated in detail. The aquatic toxicity was established using Daphnia magna . All surfactants yielded EC(50) values considerably higher than that reported for cationic surfactants based on quaternary ammonium groups. Finally, their biodegradability was evaluated using the CO(2) headspace test (ISO 14593). These lysine derivatives showed high levels of biodegradation under aerobic conditions and can be classified as "readily biodegradable compounds".


Chiral growth of adherent filopodia.
Adherent filopodia are elongated finger-like membrane protrusions, extending from the edges of diverse cell types and participating in cell adhesion, spreading, migration, and environmental sensing. The formation and elongation of filopodia are driven by the polymerization of parallel actin filaments, comprising the filopodia cytoskeletal core. Here, we report that adherent filopodia, formed during the spreading of cultured cells on galectin-8-coated substrates, tend to change the direction of their extension in a chiral fashion, acquiring a left-bent shape. Cryoelectron tomography examination indicated that turning of the filopodia tip to the left is accompanied by the displacement of the actin core bundle to the right of the filopodia midline. Reduction of the adhesion to galectin-8 by treatment with thiodigalactoside abolished this filopodia chirality. By modulating the expression of a variety of actin-associated filopodia proteins, we identified myosin-X and formin DAAM1 as major filopodia chirality promoting factors. Formin mDia1, actin filament elongation factor VASP, and actin filament cross-linker fascin were also shown to be involved. Thus, the simple actin cytoskeleton of filopodia, together with a small number of associated proteins are sufficient to drive a complex navigation process, manifested by the development of left-right asymmetry in these cellular protrusions.